Abstract
INTRODUCTION: Developmental and epileptic encephalopathy 9 (DEE9) is caused by pathogenic variants in the PCDH19 gene. The clinical features include early-onset seizures that are often provoked by fever and display clustered seizures, mild to profound intellectual disability, autistic traits, and behavioral disturbances. DEE9 is characterized by an unusual X-linked pattern where heterozygous females or rarely mosaic hemizygous males are affected, but hemizygous males and homozygous females are asymptomatic. In recent years, an increasing number of female and male patients with PCDH19-related epilepsy and symptoms have been reported. METHODS: Here, we report two additional female patients with DEE9 who are siblings. After analyzing karyotype testing results, whole-exome sequencing (WES) was performed for the proband. Then, Sanger sequencing was carried out for proband, her affected sister, and parents. RESULTS: Sequencing results revealed that our two patients had a heterozygous frameshift variant (NM_001184880.2: c.1091delC, p.P364Rfs*4) in the PCDH19 gene. We also reviewed previously reported cases with this mutation in detail. CONCLUSION: This is the first report of germline mosaicism in the PCDH19 gene in the Iranian population and expanded the phenotypic spectrum of DEE9. Genetic testing has become an effective way of determining the diagnosis. Parental germline mosaicism should be considered when providing genetic counseling for X-linked/autosomal dominant disorders. This report also emphasizes the importance of considering prenatal diagnosis (PND) in such cases.